title: Desmosterol and DHCR24: unexpected new directions for a terminal step in cholesterol synthesis.
abstract: 3β-Hydroxysterol Δ(24)-reductase (DHCR24) catalyzes the conversion of desmosterol to cholesterol. This ultimate step of cholesterol biosynthesis appears to be remarkable in its diverse functions and the number of diseases it is implicated in from vascular disease to Hepatitis C virus (HCV) infection to cancer to Alzheimer's disease. This review summarizes the present knowledge on the DHCR24 gene, sterol Δ(24)-reductase protein and the regulation of both. In addition, the functions of desmosterol, DHCR24 and their roles in human diseases are discussed. It is apparent that DHCR24 exerts more complex effects than what would be expected based on the enzymatic activity of sterol Δ(24)-reduction alone, such as its influence in modulating oxidative stress. Increasing information about DHCR24 membrane association, processing, enzymatic regulation and interaction partners will provide further fundamental insights into DHCR24 and its many and varied biological roles.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Eser J
authors.initials: EJ
authors.lastname: Zerenturk
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sharpe
authors.forename: Elina
authors.initials: E
authors.lastname: Ikonen
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D000015:Abnormalities, Multiple / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D003897:Desmosterol / Q000378:metabolism*; D057890:Epigenomics; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D003897:Desmosterol; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human
keywords: 3-hydroxy-3-methylglutaryl-coenzyme A reductase; 3β-Hydroxysterol Δ(24)-reductase; 3β-hydroxysterol Δ(24)-reductase; 7-dehydrocholesterol reductase; ACTH; Bloch pathway; CAR; Cholesterol; Cholesterol homeostasis; DHCR24; DHCR7; DWF1; Desmosterol; Desmosterolosis; ER; FAD; HCV; HDL; HMGCR; LXR; Mdm2; NF-Y; PXR; SRE; SREBP; SREBP-cleavage activating protein; Scap; Seladin-1; Sp1; TH; adrenocorticotropic hormone; constitutive androstane receptor; dwarf 1; endoplasmic reticulum; flavin adenine dinucleotide; hepatitis C virus; high-density lipoprotein; liver X receptor; mouse double minute 2 homolog; nuclear factor Y; pregnane X receptor; selective Alzheimer’s disease indicator-1; specificity protein 1; sterol regulatory element; sterol regulatory element binding protein; thyroid hormone